Title

Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Document Type

Journal Article

Publication Title

Alzheimer's and Dementia

Volume

18

Issue

6

First Page

1141

Last Page

1154

PubMed ID

34494715

Publisher

Wiley

School

School of Medical and Health Sciences

RAS ID

38867

Funders

Australian Alzheimer’s Research Foundation Swedish Research Council,Grant / Award Number: #2018-02532 European Research Council,Grant / Award Number: #681712 Swedish State Support for Clinical Research, Grant / Award Number: #ALFGBG-720931 Alzheimer Drug Discovery Foundation (ADDF), USA, Grant / Award Number: #201809-2016862, #RDAPB-201809-2016615 UK Dementia Research Institute at UC Swedish Alzheimer Foundation, Grant / Award Number: #AF-742881 Hjärnfonden, Sweden, Grant / Award Number: #FO2017-0243

Comments

Chatterjee, P., Pedrini, S., Ashton, N. J., Tegg, M., Goozee, K., Singh, A. K., ... & Martins, R. N. (2022). Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease. Alzheimer's & Dementia, 18(6), 1141-1154. https://doi.org/10.1002/alz.12447

Abstract

Introduction:

This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).

Methods:

Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ−) or presence (Aβ+) of brain amyloidosis.

Results:

Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ− CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ− CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC ( > 90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ− CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.

Discussion:

These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.

DOI

10.1002/alz.12447

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